The present invention relates to compositions of matter for reducing or maintaining intraocular pressure, and, more particularly, to a method and composition for reducing or maintaining intraocular pressure involving the administration of a composition of matter containing a prostaglandin-like 7-oxabicyclo derivative in a pharmaceutically acceptable carrier.
The compositions and method of the present invention are particularly useful for the management of glaucoma, a disease of the eye characterized by increased intraocular pressure. On the basis of its etiology, glaucoma has been classified as primary or secondary. For example, primary glaucoma in adults, e.g., congenital glaucoma, may be either chronic open-angle, or acute or chronic angle-closure. Secondary glaucoma results from pre-existing ocular disease, typically such as uneitis, intraocular tumor or an enlarged cataract.
The causes of primary glaucoma are not yet known. The increased intraocular tension is related to an imbalance between production and outflow of the aqueous humor, typically due to obstruction to outflow. In chronic open-angle glaucoma, the anterior chamber and its anatomic structures appear normal but draining of the aqueous humor is impeded. In acute and chronic angle-closure glaucoma, the anterior chamber is shallow, the filtration angle is narrowed and the iris may obstruct the trabecular meshwork at the entrance of the canal of Schlemm. Dilation of the pupil may push the root of the iris forward against the angle or may produce pupillary block and thus precipitate an acute attack. Eyes with narrow anterior chamber angles are predisposed to acute angle-closure glaucoma attacks of varying degrees of severity.
Secondary glaucoma is caused by an interference with the flow of aqueous humor from the posterior chamber into the anterior chamber to the canal of Schlemm. Inflammatory disease of the anterior segment may prevent aqueous escape by causing complete posterior synechia in iris bombe, and may plug the draining channel with exudates. Other common causes are intraocular tumors, enlarged cataracts, central retinal vein occlusion, trauma to the eye, operative procedures and intraocular hemorrhage.
Considering all types together, glaucoma occurs in about 2% of all patients over the age of 40, and may be asymptomatic for years before progressing to rapid loss of vision. In cases where surgery is not indicated, systemic and topical .beta.-adrenoceptor antagonists have traditionally been the drugs of choice for treatment. Certain eicosanids, particularly various prostaglandins, have been reported to possess hypotensive activity. However, prostaglandin ocular hypotensives generally suffer from the disadvantage of inducing conjunctival hyperemia of varying severity and duration, smarting and foreign body sensation, as well as presenting solubility problems in certain ophthalmically advantageous carriers.
The present invention relates to certain prostaglandin-like 7-oxabicyclo derivatives which may be formulated in a pharmaceutically acceptable vehicle, and ophthalmic uses of those prostaglandin compositions. The formulations of the present invention have been discovered to retain an intraocular pressure reducing effect similar to that of the related prostaglandin, but with elimination of the aforementioned undesirable side effects.
The compounds are known (U.S. Pat. No. 4537981) and may be synthesized by methods known in the art for the synthesis of compounds of analogous structure. They have been previously reported as having potential utility in cardiovascular and respiratory diseases. Their safe use as ocular hypotensives is unexpected and previously unrecognized.